Bovine spongiform encepalopathy (BSE), scrapie of sheep, Kuru and Creutzfeldt-Jakob disease (CJD) of humans are only a few examples of a group of neurodegenerative disorders named transmissible spongiform encepalopathies (TSE) which are characterized by loss of motor control, dementia, paralysis, blindness, wasting and eventually death. These diseases may be inherited or sporadic. A risk of contracting TSE for humans is believed to be through food products derived from BSE-infected cattle. Another transmission risk is possible infection through human blood and blood products which originated from TSE-infected donors.
Recently, it was shown that these fatal neurodegenerative diseases are caused by a newly discovered infectious pathogen named prion protein (PrP) (Prusiner S. B., P.N.A.S. 95, 13363–13383, 1998). More precisely, the accumulation of an infectious isoform of PrP into amyloid plaques results in the development of the disease. Different isoforms of PrP have been identified as a normal cellular form (PrPc) and a highly infectious scrapie form (PrPSc). The PrPSc form of the protein was found to be protease and detergent resistant, while PrPc has been shown to be sensitive to the conventional treatment processes causing protein degradation and denaturation. Although identical in amino acid sequence, the two proteins have been shown to have different conformational characteristics with PrPc containing more α-helical structure than its infectious counterpart. Nevertheless, there has been no effective method of discriminating between the two proteins by the way of immunoreagents. Only recently, plasminogen was recognized as the first naturally occurring PrPSc-binding protein that can distinguish between PrPc and PrPSc (Fischer M. B., Nature, 406, 479–483, 2000).
A handful of blood-screening test methods are in different stages of development. Several methods appear to have threshold PrP detection sensitivities within the range of what might be encountered in the blood of infected individuals, but none has yet been shown to be capable of detecting PrPSc in the blood of human beings who are incubating CJD (Brown et al., J. Lab. Clinic. Med. 137 (1), 5–13, 2001). In addition, the methods and instruments used for detection have two critical limitations: inherent insensitivity of the method and a minimum specimen volume to be tested by the instrument.
Currently, there are no commercial non-invasive assays that allow detection of prions in infected individuals prior to the development of clinical symptoms of disease. The few tests that are in use are able to detect prions in brain tissue and the spinal cord only and are largely used on animals and humans in their post-mortem state.
In the pre-clinical phase of prion infection in experimentally infected rodents, it was identified that PrPSc infectivity was closely associated with blood buffy coat, leucocyte, platelet and plasma fractions.